The diepoxide functionality appears to conver tumor-inhibitory active on several classes of compounds. Although attempts have been made to understand the mode of action of these compounds in terms of their selective "alkylating ability" toward certain biological nucleophiles (e.g., DNA) and to understand the structural factors which govern the anti-tumor activity of these oxiranes, more diepoxides must be studied before firm conclusions can be reached. The recent isolation and characterization of several antitumor and antibiotic diepoxides of plant origin have stimulated considerable interest in preparing sufficient quantities of these compounds and of their structural and stereochemical analogs so that thorough and broad biological screening can be performed and so that rational structure activity correlations ultimately can be made. Crotepoxide has recently been isolated from the fruits of Croton macrostachys, which grows in Ethiopia, and has been found to have significant tumor inhibitory activity against Lewis lung carcinoma in mice and Walker intromolecular carcinosarcoma in rats. The structure and absolute stereochemistry of this plant-derived tumor inhibitor were established by spectral and x-ray crystallographic evidence. Although several attemts have been made to synthesize Crotepoxide in the laboratory, no successful preparation of this highly functionalized diepoxycyclohexane system has been reported. The primary goal of this project is to synthesize Crotepoxide in a few steps from readily available starting materials and thus to produce enough of this substance for broad biological screening. The secondary goals of this projects are (1) to study the stereochemistry and regiochemistry of allylic bromination of unsymmetrically substituted cyclohexenes and (2) to examine the effect of alkyl substituents on the rate and position of valence tautomerism of syn-benzene dioxides. The spectroscopic and chemical methods to be used are those of modern synthetic organic chemistry. The key synthetic steps involve (1) cis-hydroxylation of a symmetrical 1,4-cyclohexadiene, (2) allylic 1,4-debromination of a substituted cyclohexens, (3) double epoxide formation from a bis-bromohydrin, and (4) stereospecific and regiospecific trans-acetoxylation of a diepoxycyclohexene using the Prevost procedure. Modification of this synthetic scheme to prepare analogs of Crotepoxide is discussed.